The invention relates to a method and a apparatus for the targeted coating process of catheters or balloon catheters. The term “catheters” herein means catheters exclusive of a balloon.
The treatment of stenosises is provided by placing stents and/or by using so called balloon catheters in order to dilate the respective vessels again. Here, in recent years considerable results have been achieved. Because of that, in many cases a dilatation of the vessel lumen exceeding 90% of the value before the constriction has started can be achieved.
However, in the past a renewed constriction (restenosis) has happened with numerous patients after a few months. Mostly, this is a consequence of the immoderate proliferation, especially of the smooth muscle cells, due to the forcible dilatation of the vessel walls. After healing up the injury the proliferation thereof does not stop immediately, thus frequently leading to a restenosis. One can inhibit this effect by coating the stents and the balloon catheters with an anti-restenosis active agent.
As a rule, the balloon catheters and stents have to travel a long path inside the vessels until they reach the location of the vessel constriction. Here, one is faced with the problem to prevent a premature separation of the active agents prior to reaching the destination and to ensure that the active agent is available in a predefined quantity at the location of the vessel constriction.
With the exclusive application of balloon catheters the contact time with the vessel wall only lasts some seconds to a few minutes during the dilatation of the balloon which aggravates the situation. Thus, it is necessary for the existing contact area to completely be used if possible by means of a uniform coating process, and for the active agents to be provided with a high bio-availability.
The stenosis of arteries is often combined with massive calcification. The vessels concerned can only be dilated to their original lumen again by means of very high pressure. For this purpose, a pressure-resistant balloon is inserted which forms into a stable cylinder through dilatation closely bearing against the vessel wall and pressing the active agents applied from the outside with appropriately high pressure against the vessel walls.
With the same method a local medicament dose can also be carried out without a dilatation of the vessels being necessary. Examples can be found with alterations of the vessel wall which are not associated with stenosis (e.g. vulnerable plaques, deposited thrombi). Other examples include the treatment of vessels by mechanical means or by thermal methods. In these cases, an overstretching of the vessel walls and a laceration combined therewith are not desired. As a result, the balloons which are used do not either bear against the irregular vessel walls completely and the active agents will be pressed against these with lower pressure.
In numerous publications there are proposed solutions which should prevent the premature separation of the active agents with the stents. One possibility consists in housing the active agent in small cavities and by preventing the premature separation by means of a protective coating (US 2004/0071861 A, WO 2003/035131 A). Likewise, described is the possibility to apply an inflexible final coating over the active agent layer which breaks open with the expansion (WO 2000/45744 A1). By contrast, DE 102007010354 A1 describes a combination of the active agent layer and absorbable sacrificial coating layer situated thereabove.
Coatings with active agents have also been described with balloon catheters. However, due to the greater surface and the folded structure they are more difficult to implement. Beyond that, an immediate release of the active agents from the catheter to the vessel walls is necessary as a result of the short contact time.
The possibility of reliably preventing restenosis even during the short contact of the balloon catheters with the blood vessels has been disclosed for the first time in WO 2002/076509 A2. Therein a balloon catheter is described which releases the active agent immediately in a bio-available form during contact with the vessel wall.
In numerous publications of the prior art there are described active agents and complex combinations from very diverse materials which are suitable for coating stents and/or balloon catheters.
In EP 0519063 B1 there is disclosed the possibility to coat a folded balloon being initially expanded and then deflated again with micro capsules in which a pharmaceutical agent can be included. A disadvantage of this embodiment lies in the fact that the majority of the micro capsules is separated from the balloon surface while inserting the balloon catheter into a vessel, and that only the capsules in the folds reach the destination. Thus, the quantity of the micro capsules being available during the expansion and hence the separated agent quantity is not known.
WO 2007/090385 A2 discloses a possibility of providing the folds of a balloon catheter specifically with an agent. With this embodiment the entire agent stock reaches the destination.
In the aforementioned two embodiments (EP 0519063 B1 and WO 2007/090385 A2) the agent is only transferred via one part of the balloon surface to the vessel walls. In this manner, it cannot be made certain that the agent in necessary quantity does reach all affected places of the vessel wall.
In WO 2004/006976 A, lipophilic pharmaceutical preparations are applied onto a structured, especially rough, surface of the expanded balloon through spraying, immersion or absorbing. By means of a lipophilic layer between the pharmaceutical preparation and the balloon surface the separation of the agent should be facilitated.
The most often described solutions for coating catheters and balloon catheters are based on a substrate decelerating the release of the agents. However, in the course of this the contact time between the balloon surface and ambient tissue is relatively short.
In contrast to this, DE 102007036685 A1 discloses the coating process of a balloon catheter in such a manner that at least one agent is immediately released. very diverse compositions functioning as agents and transport mediators are disclosed therein.
In WO 2008/086794 A2 there is generally disclosed the coating process of catheter balloons by means of a volumeter and a dispensing device. Thereby a great many different methods for the coating process are used. However, it is known that not all methods described therein result in a surface having the same characteristics in quality.
In U.S. Pat. No. 6,322,847 B1 there is disclosed a possibility of removing surplus portions resulting from the coating process by means of a gas jet. But it is more useful to avoid such surplus portions already during the coating process, and thus to render superfluous a later treatment. Drying the coating during the treatment with the gas jet cannot completely be avoided. Consequently, the calibration of the system is very expensive because, on the one hand, a gas jet which is too weak cannot remove the surplus portions of the layer which have become more solid, and, on the other hand, a gas jet which is too strong can damage the layer in such a manner that the object to be coated is not completely covered any longer.
US 200610029720 A1 discloses a method of coating a medical device by applying the coating solution onto the top end of the vertically set up medical device. Then, the distribution takes place by means of flow processes due to gravity. One advantage of the invention is the good possibility of automation. With medical devices, in particular stents, uniform coating and, in particular, a very uniform distribution of the contained agents across the surface is of great significance. However, uniform distribution of the coating solution represents a problem with this method. This particularly applies to heavily structured objects such as stents or balloon catheters. The formation of projections and drops cannot practically be avoided with the flow technique, and additional methods, such as e.g. according to U.S. Pat. No. 6,322,847 B1, have to be used.
U.S. Pat. No. 6,406,754 B2 and U.S. Pat. No. 6,254,921 B1 describe a device and a method for coating a tubular or wire-like medical device including the possibility to leave out such regions which should not obtain any coating. With this method it is also possible to apply various coatings onto different regions of the medical device. For this purpose, a chamber is used which encloses the medical device at the ends such that coating solution is not allowed to escape. As a result, coating can take place through feeding and draining off the coating solution in the chamber or by means of a relative motion of the chamber and medical device. This approach has just several disadvantages. The impermeable seal of the chamber at the ends is technologically very expensive because many of these products are either heavily structured, e.g. stents, or have folds of such as e.g. balloon catheters. During a relative motion of the chamber and medical device the new coating, already existing coatings or even the medical device itself can be damaged the impermeable seal. Likewise, residual quantities remaining in the chamber and damages of the coating at the sealing positions represent a problem during opening the chamber.
In US 2007/0128343 A1 there is disclosed a possibility of having two spray nozzles by means of which two different coating solutions can be applied. A spraying method has several disadvantages which are not overcome by the present publication. For a uniform coating it is necessary to move the spray nozzles and the object to be coated relative to the longitudinal axis and to carry out a rotational motion of the object or an adequate motion of the spray nozzles as well. The well-defined quantity of the substances applied on the objects is just hard to guarantee as always a part of the substances do not arrive on the object to be coated during spraying. However, this is of great significance exactly with medically effective components.
Practicable compositions of coating solutions are described in detail in the prior art documents. The methods for coating are primarily presented in terms of calculated filling of the folds of the catheter balloon and/or applying a specific quantity of the coating solution.
The same way, there are disclosed many possibilities of designing the surface of the balloon, be that through structuring or by means of an additional treatment.
Common to prior art documents is that the effect of the coating method on the structure and the quality of the surface is not sufficiently taken into account. Likewise, the ambient conditions and further process parameters having a decisive influence on the quality properties of the surfaces are only insufficiently represented.